Clinical characteristics and 28-d outcomes of bacterial infections in patients with hepatitis B virus-related acute-on-chronic liver failure

Table 1 Baseline characteristics and laboratory results of the overall study collective

Characteristic	Total (n = 199)	AD (n = 40)	ACLF (n = 159)	χ2/t/Z value	P value
Age (yr)	48.0 ± 10.9	49.0 ± 12.1	47.7 ± 10.5	0.667	0.506
Male (%)	170 (85.4)	34 (85.0)	136 (85.5)	0.007	0.932
Cirrhosis (%)	172 (86.4)	35 (87.5)	137 (86.2)	0.049	0.825
SIRS (%)	90 (45.2)	15 (37.5)	75 (47.2)	1.206	0.272
Temperature (°C)	37.1 (36.6, 38.0)	37.4 (36.6, 38.2)	37.1 (36.6, 38.0)	-0.500	0.617
MAP (mmHg)	87.8 ± 14.2	86.6 ± 14.4	88.1 ± 14.2	-0.580	0.562
Invasive catheterization (%)	38 (19.1)	5 (12.5)	33 (20.8)	1.410	0.235
Multiple sites of BIs (%)	36 (18.1)	6 (15.0)	30 (18.9)	0.323	0.570
HBV DNA (log10 IU/ml)	4.1 (2.5, 6.0)	3.4 (1.2, 5.7)	4.4 (2.6, 6.2)	-1.259	0.208
WBC (×109/L)	8.7 (6.0, 13.6)	8.0 (4.7, 11.3)	8.9 (6.1, 14.0)	-1.477	0.140
NEUT (×109/L)	6.7 (4.1, 11.1)	5.9 (3.6, 8.6)	6.9 (4.2, 11.3)	-1.261	0.207
HGB (g/L)	107.8 ± 24.9	108.2 ± 25.0	107.7 ± 24.9	0.129	0.897
PLT (×109/L)	63.0 (42.0, 91.0)	60.0 (47.0, 90.3)	63.0 (41.0, 96.0)	-0.092	0.927
ALB (g/L)	27.0 (24.0, 31.0)	26.5 (23.0, 31.5)	28.0 (25.0, 31.0)	-1.088	0.277
TBIL (μmol/L)	330.6 ± 158.4	226.5 ± 142.9	356.7 ± 151.6	-4.909	< 0.001
DBIL (μmol/L)	227.8 ± 109.4	159.0 ± 100.6	245.2 ± 104.9	-4.684	< 0.001
ALT (IU/L)	81.0 (38.0, 183.0)	48.0 (29.3, 129.5)	87.0 (42.0, 246.0)	-2.774	0.006
AST (IU/L)	119.0 (71.0, 221.0)	73.5 (60.0, 175.3)	126.0 (82.0, 234.0)	-2.549	0.011
ALP (IU/L)	141.0 (106.0, 188.0)	133.0 (101.0, 181.5)	143.0 (111.0, 192.0)	-1.184	0.236
GGT (IU/L)	50.0 (33.0, 77.0)	46.0 (29.3, 70.8)	54.0 (34.0, 78.0)	-1.193	0.233
Cr (μmol/L)	101.0 (80.0, 148.0)	83.0 (72.0, 96.0)	112.0 (84.0, 162.0)	-4.480	< 0.001
Na (mmol/L)	133.0 (130.0, 136.0)	134.0 (130.3, 136.0)	133.0 (130.0, 136.0)	-0.916	0.360
INR	2.2 (1.7, 2.8)	1.6 (1.4, 2.0)	2.3 (1.9, 3.1)	-6.429	< 0.001
PTA (%)	30.0 ± 13.1	42.2 ± 12.6	26.9 ± 11.4	7.455	< 0.001
CRP (mg/L)	18.3 (11.1, 40.4)	25.1 (13.0, 43.0)	17.5 (10.4, 40.1)	-1.112	0.266
PCT (ng/mL)	1.2 (0.6, 2.3)	1.1 (0.4, 2.1)	1.2 (0.7, 2.4)	-1.182	0.237
Ascites (%)	192 (96.5)	37 (92.5)	155 (97.5)	1.101	0.126
AKI (%)	95 (47.7)	9 (22.5)	86 (54.1)	12.782	< 0.001
HE (%)	106 (53.3)	6 (15.0)	100 (62.9)	29.449	< 0.001
AVB (%)	39 (19.6)	5 (12.5)	34 (21.4)	1.601	0.206
COSSH-ACLF scores	6.5 (5.9, 7.5)	5.4 (5.2, 5.9)	6.8 (6.1, 7.9)	-7.851	< 0.001

χ²/t/Z value and P value represent the comparison between the AD and ACLF groups. AD: Acute decompensation; ACLF: Acute-on-chronic liver failure; SIRS: Systemic inflammation response syndrome; MAP: Mean arterial pressure; BIs: Bacterial infections; HBV: Hepatitis B virus; WBC: White blood cells; NEUT: Neutrophil count; HGB: Hemoglobin; PLT: Platelet; ALB: Albumin; TBIL: Total bilirubin; DBIL: Direct bilirubin; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; ALP: Alkaline phosphatase; GGT: Gamma-glutamyl transpeptidase; Cr: Creatinine; Na: Sodium; INR: International normalized ratio; PTA: Prothrombin activity; CRP: C-reactive protein; PCT: Procalcitonin; AKI: Acute kidney injury; HE: Hepatic encephalopathy; AVB: Acute variceal bleed; COSSH: Chinese Group on the Study of Severe Hepatitis B.

Table 2 Characteristics of all the 241 episodes of bacterial infections in the overall study collective

Characteristic	Total (n = 241)	AD (n = 47)	ACLF (n = 194)	χ2 value	P value
Source of acquisition
CA BIs (%)	35 (14.5)	9 (19.1)	26 (13.4)	1.007	0.316
HCA BIs (%)	117 (48.5)	27 (57.4)	90 (46.4)	1.851	0.174
Nosocomial BIs (%)	89 (36.9)	11 (23.4)	78 (40.2)	4.586	0.032
Site of BIs
Pneumonia (%)	93 (38.6)	14 (29.8)	79 (40.7)	1.909	0.167
SBP (%)	87 (36.1)	20 (42.6)	67 (34.5)	1.054	0.305
BSI (%)	32 (13.3)	6 (12.8)	26 (13.4)	0.013	0.908
Other BIs (%)	29 (12.0)	7 (14.9)	22 (11.3)	0.451	0.502
SBE (%)	11 (4.6)	3 (6.4)	8 (4.1)	0.076	0.782
UTI (%)	7 (2.9)	3 (6.4)	4 (2.1)	1.207	0.272
Cellulitis (%)	2 (0.8)	0 (0.0)	2 (1.0)	Fisher	1.000
Unproven BIs (%)	9 (3.7)	1 (2.1)	8 (4.1)	0.048	0.827

χ² value and P value represent the comparison between the AD and ACLF groups. BIs: Bacterial infections; AD: Acute-on-chronic liver failure; ACLF: Acute decompensation; CA: Community-acquired; HCA: Healthcare-associated; SBP: Spontaneous bacterial peritonitis; BSI: Bloodstream infection; SBE: Spontaneous bacterial empyema; UTI: Urinary tract infection.

Table 3 Relationship between site of bacterial infections and grade of acute-on-chronic liver failure

Site of BIs	AD (n = 47)	ACLF-1 (n = 92)	ACLF-2 (n = 53)	ACLF-3 (n = 49)	χ2 value	P value
SBP (%)	20 (42.6)	39 (42.4)	16 (30.2)	12 (24.5)	6.093	0.107
Pneumonia (%)	14 (29.8)	36 (39.1)	20 (37.7)	23 (46.9)	3.006	0.391
BSI (%)	6 (12.8)	9 (9.8)	10 (18.9)	7 (14.3)	2.468	0.481
Other BIs (%)	7 (14.9)	8 (8.7)	7 (13.2)	7 (14.3)	1.635	0.651

χ² value and P value represent overall comparison among the four groups. BIs: Bacterial infections; AD: Acute decompensation; ACLF: Acute-on-chronic liver failure; SBP: Spontaneous bacterial peritonitis; BSI: Bloodstream infection.

Table 4 Bacterial identification and detection of multidrug-resistant organisms in patients with acute-on-chronic liver failure

Bacterial isolate	Total Bis (n = 61)	Pneumonia (n = 12)	SBP (n = 19)	BSI (n = 26)	Other Bis (n = 4)
Source of acquisition
CA BIs (/total, %)	10 (16.4)	0 (0)	4 (21.1)	6 (23.1)	0 (0)
HCA BIs (/total, %)	27 (44.3)	5 (41.7)	8 (42.1)	11 (42.3)	3 (75.0)
Nosocomial BIs (/total, %)	24 (39.3)	7 (58.3)	7 (36.8)	9 (34.6)	1 (25.0)
Gram-negative bacteria (/total, %)	51 (83.6)	12 (100.0)	16 (84.2)	20 (76.9)	3 (75.0)
Escherichia coli (/total, %)	27 (44.3)	1 (8.3)	14 (73.7)	10 (38.5)	2 (50.0)
Klebsiella pneumoniae (/total, %)	14 (23.0)	5 (41.7)	2 (10.5)	6 (23.1)	1 (25.0)
Pseudomonas aeruginosa (/total, %)	4 (6.6)	4 (33.3)	0 (0)	0 (0)	0 (0)
Acinetobacter baumannii (/total, %)	2 (3.3)	0 (0)	0 (0)	2 (7.7)	0 (0)
Other (/total, %)	4 (6.6)	2 (16.7)	0 (0)	2 (7.7)	0 (0)
Gram-positive bacteria (/total, %)	10 (16.4)	0 (0)	3 (15.8)	6 (23.1)	1 (25.0)
Enterococcus faecium (/total, %)	5 (8.2)	0 (0)	2 (10.5)	3 (11.5)	0 (0)
Staphylococcus aureus (/total, %)	2 (3.3)	0 (0)	0 (0)	2 (7.7)	0 (0)
Staphylococcus epidermidis (/total, %)	2 (3.3)	0 (0)	0 (0)	1 (3.8)	1 (25.0)
Other (%) (/total, %)	1 (1.6)	0 (0)	1 (5.3)	0 (0)	0 (0)
MDROs (/total, %)	18 (29.5)	3 (25.0)	5 (26.3)	8 (30.8)	2 (50.0)
Multidrug-resistant Gram-negative organisms (/Gram-negative bacteria, %)	10 (19.6)	3 (25.0)	3 (18.8)	3 (15.0)	1 (33.3)
Multidrug-resistant Gram-positive organisms (/Gram-positive bacteria, %)	8 (80.0)	0 (0)	2 (66.7)	5 (83.3)	1 (100.0)

BIs: Bacterial infections; SBP: Spontaneous bacterial peritonitis; BSI: Bloodstream infection; CA: Community-acquired; HCA: Healthcare-associated; MDROs: Multidrug-resistant organisms.

Table 5 Independent predictors of 28-d outcomes in hepatitis B virus-related acute-on-chronic liver failure patients combined with bacterial infections

Variable	Survivors (n = 58)	Nonsurvivors (n = 99)	Univariate Cox regression		Multivariate Cox regression
			HR (95%CI)	P value	HR (95%CI)	P value
Age (yr)	45.5 ± 9.7	49.3 ± 10.7	1.023 (1.005-1.042)	0.013
Male (%)	53 (91.4)	82 (82.8)	0.693 (0.410-1.170)	0.170
Cirrhosis (%)	50 (86.2)	85 (85.9)	0.956 (0.543-1.684)	0.877
SIRS (%)	17 (29.3)	58 (58.6)	2.214 (1.480-3.310)	< 0.001
Temperature (°C)	37.1 (36.6, 38.0)	37.1 (36.6, 38.0)	1.055 (0.861-1.293)	0.604
MAP (mmHg)	86.9 ± 11.4	88.9 ± 15.5	1.003 (0.987-1.019)	0.696
Invasive catheterization (%)	6 (10.3)	26 (26.3)	2.026 (1.290-3.181)	0.002	2.173 (1.320-3.579)	0.002
Grade of ACLF
ACLF-1 (%)	44 (75.9)	35 (35.4)	Reference	< 0.001
ACLF-2 (%)	12 (20.7)	29 (29.3)	1.977 (1.205-3.243)	0.007
ACLF-3 (%)	2 (3.4)	35 (35.4)	4.648 (2.862-7.548)	< 0.001
HBV DNA (log10 IU/ml)	3.6 (2.3, 5.5)	4.7 (2.8, 6.6)	1.083 (0.997-1.177)	0.060
WBC (×109/L)	7.5 (5.6, 11.3)	10.4 (6.9, 15.0)	1.054 (1.022-1.088)	0.001
NEUT (×109/L)	5.4 (3.4, 8.6)	8.5 (5.1, 12.7)	1.058 (1.023-1.094)	0.001
HGB (g/L)	105.0 ± 21.6	109.3 ± 26.3	1.003 (0.994-1.011)	0.516
PLT (×109/L)	64.0 (46.8, 88.5)	63.0 (40.0, 98.0)	1.000 (0.995-1.005)	0.984
ALB (g/L)	28.0 (25.0, 31.0)	28.0 (23.0, 31.0)	0.984 (0.945-1.024)	0.435
TBIL (μmol/L)	353.6 ± 130.9	356.4 ± 163.7	1.000 (0.999-1.001)	0.836
DBIL (μmol/L)	257.4 ± 88.3	236.8 ± 113.7	0.998 (0.996-1.000)	0.091
ALT (IU/L)	76.5 (35.3, 127.8)	103.0 (49.0, 352.0)	1.001 (1.000-1.001)	0.003
AST (IU/L)	118.0 (71.0, 165.0)	136.0 (85.0, 367.0)	1.001 (1.000-1.001)	< 0.001
ALP (IU/L)	158.5 (125.8, 211.3)	137.0 (99.0, 179.0)	1.000 (0.998-1.001)	0.721
GGT (IU/L)	49.0 (35.8, 78.8)	56.0 (33.0, 78.0)	0.999 (0.995-1.004)	0.821
Cr (μmol/L)	98.5 (79.5, 126.3)	122.0 (87.0, 196.0)	1.002 (1.001-1.003)	0.001
Na (mmol/L)	133.0 (130.0, 136.0)	132.0 (128.0, 136.0)	0.996 (0.962-1.031)	0.830
INR	1.9 (1.7, 2.3)	2.6 (2.1, 3.3)	1.762 (1.487-2.089)	< 0.001
PTA (%)	33.2 ± 11.1	23.3 ± 9.9	0.937 (0.917-0.957)	< 0.001	0.967 (0.941-0.993)	0.015
CRP (mg/L)	20.5 (13.2, 43.4)	16.2 (8.9, 39.6)	0.998 (0.991-1.005)	0.530
PCT (ng/mL)	1.2 (0.8, 1.8)	1.2 (0.6, 2.9)	1.017 (1.002-1.033)	0.025
Ascites (%)	57 (98.3)	96 (97.0)	0.578 (0.183-1.828)	0.351
AKI (%)	24 (41.4)	61 (61.6)	2.777 (1.734-4.449)	< 0.001	2.187 (1.259-3.799)	0.005
HE (%)	23 (39.7)	76 (76.8)	1.635 (1.089-2.454)	0.018
AVB (%)	8 (13.8)	26 (26.3)	1.476 (0.942-2.312)	0.089
Pneumonia (%)	20 (34.5)	59 (59.6)	1.831 (1.222-2.744)	0.003
SBP (%)	34 (58.6)	33 (33.3)	0.553 (0.364-0.842)	0.006
BSI (%)	6 (10.3)	20 (20.2)	1.661 (1.016-2.715)	0.043	2.339 (1.384-3.952)	0.002
Other BIs (%)	4 (6.9)	16 (16.2)	1.488 (0.870-2.544)	0.146
Multiple sites of BIs (%)	6 (10.3)	24 (24.2)	1.797 (1.132-2.852)	0.013
MDROs (%)	4 (6.9)	11 (11.1)	1.401 (0.728-2.696)	0.313
CA BIs (%)	4 (6.9)	13 (13.1)	1.537 (0.857-2.757)	0.149
HCA BIs (%)	24 (41.4)	47 (47.5)	1.046 (0.705-1.553)	0.821
Nosocomial BIs (%)	30 (51.7)	39 (39.4)	0.804 (0.537-1.204)	0.290
COSSH-ACLF Scores	6.1 (5.8, 6.7)	7.4 (6.6, 8.7)	1.704 (1.498, 1.937)	< 0.001	1.371 (1.127-1.666)	0.002

SIRS: Systemic inflammation response syndrome; MAP: Mean arterial pressure; ACLF: Acute-on-chronic liver failure; HBV: Hepatitis B virus; WBC: White blood cells; NEUT: Neutrophil count; HGB: Hemoglobin; PLT: Platelet; ALB: Albumin; TBIL: Total bilirubin; DBIL: Direct bilirubin; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; ALP: Alkaline phosphatase; GGT: Gamma-glutamyl transpeptidase; Cr: Creatinine; Na: Sodium; INR: International normalized ratio; PTA: Prothrombin activity; CRP: C-reactive protein; PCT: Procalcitonin; AKI: Acute kidney injury; HE: Hepatic encephalopathy; AVB: Acute variceal bleed; SBP: Spontaneous bacterial peritonitis; BSI: Bloodstream infection; BIs: Bacterial infections; MDROs: Multidrug-resistant organisms; CA: Community-acquired; HCA: Healthcare-associated; COSSH: Chinese Group on the Study of Severe Hepatitis B.